Treatment Resistant Depression (TRD)NCT07329153
Neuronavigated aiTBS for TRD
A study testing aiTBS in people with Treatment Resistant Depression (TRD), run by University of Texas Southwestern Medical Center at 3 sites in United States.
Trial summary
The purpose of this study is to confirm the efficacy of two recently introduced repetitive transcranial magnetic stimulation (rTMS) interventions - accelerated intermittent theta-burst stimulation (aiTBS) and individualized neuronavigation - in treatment-resistant depression (TRD). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Treatment Resistant Depression (TRD)
- What is being tested?
- aiTBS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 247 participants
- Where
- 3 sitesUnited States
- Study dates
- Jul 2026to Sep 2031
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age: 18 to 65 years at the time of consent
- Diagnosis: Current major depressive episode (MDE) in the context of unipolar major depressive disorder (MDD), as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), confirmed by clinical psychiatric interview
- Treatment Resistance: Documented failure to respond to at least two adequate antidepressant trials on the Antidepressant Treatment History Form-Short Form (ATHF-SF). An adequate trial is defined as:
- Antidepressant medication at the maximum tolerated dose for at least 6 weeks, OR
- Evidence-based psychotherapy consisting of at least 12 sessions
- Depression Severity: Montgomery-Åsberg Depression Rating Scale (MADRS) score >19 at screening, indicating moderate to severe depression
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- Medication Stability: No changes in antidepressant medication type or dose for at least 6 weeks prior to randomization. Stable doses of permitted medications must be maintained throughout the trial
- Informed Consent: Demonstrated capacity to provide written informed consent and comply with study procedures
- Availability: Ability to attend treatment sessions for 15 consecutive workdays (approximately 90 minutes per day) and complete assessments including 4-hour evaluations at baseline and endpoint
Who cannot join
- Psychiatric Exclusions:
- Any psychiatric disorder other than MDD and comorbid anxiety disorders, including but not limited to:
- Bipolar disorder (Type I or II) (ii) Schizophrenia spectrum or other psychotic disorders (iii) Post-traumatic stress disorder (PTSD) (iv) Attention-deficit/hyperactivity disorder (ADHD) (v) Autism spectrum disorder (ASD) (vi) Obsessive-compulsive disorder (OCD) (vii) Current DSM-5 substance-use disorder (abuse or dependence) within the past 6 months, except nicotine dependence
- Personality disorder confirmed on clinical interview by an experienced study psychiatrist
- Severe suicidal ideation with structured plan (HDRS-17 item 3 score >2) or as determined by the evaluating psychiatrist
- Depressive symptoms better explained by another psychiatric condition, a medical condition, substance use, or use of medications
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- Medical and Neurological Exclusions:
- Any neurological disorder including but not limited to:
- History of seizure disorder or epilepsy (ii) Family history of epilepsy (first-degree relatives) (iii) Significant head trauma with loss of consciousness >5 minutes (iv) Stroke or transient ischemic attack (v) Neurodegenerative disorders (e.g., Parkinson's disease, multiple sclerosis, dementia) (vi) Brain tumor or intracranial mass lesion
- Unstable medical condition, defined as any condition requiring acute medical intervention or hospitalization within the past 3 months, or any condition that in the investigator's judgment could affect participant safety or study outcomes
- Contraindications to TMS/MRI:
- Presence of ferromagnetic material in or near the head, including:
- Intracranial implants (e.g., aneurysm clips, shunts, stimulators) (ii) Cochlear implants or hearing aids (iii) Metallic facial tattoos or permanent makeup (iv) Other implanted medical devices deemed unsafe for MRI/TMS
- Inability to tolerate MRI scanning due to claustrophobia or other reasons
- Medication Exclusions:
- Current use of medications known to significantly alter cortical excitability:
- Anticonvulsants (including those used for mood stabilization)
- Psychostimulants
- Lithium
- Benzodiazepines exceeding 10mg diazepam-equivalent daily dose
- Prior Treatment Exclusions:
- Electroconvulsive therapy (ECT) (≥ 6 sessions) in the current depressive episode
- Ketamine or esketamine treatment (≥ 6 sessions) in the current depressive episode
- Use of rTMS/iTBS (≥ 15 sessions) during the current depressive episode
- Vagus nerve stimulation (VNS) or deep brain stimulation (DBS) implantation
- Psychotherapy:
- Concurrent evidence-based psychotherapy is permitted if initiated >4 weeks prior to enrollment and maintained at stable frequency throughout the tria
- Other reasons:
- Unable to adhere to the study visit schedule
- Planning to relocate outside the study catchment area during the trial period
- No reliable transportation to attend study visits
- Current participation in another research study
- Current pregnancy (confirmed by in interview and clinical evaluation and, if deemed necessary, urine pregnancy test at screening)
- Currently breastfeeding
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Clinical Research Coordinator, 214-645-2991, alexus.washington@utsouthwestern.edu
Andre Russowsky Brunoni, MD PhD
Cornell University
New York, New York, 10065
Interventional Psychiatry Program Weill Cornell Medicine, 646-962-2900, tmsinfo@med.cornell.edu
Conor Liston, MD PhD
University of California at San Diego (UCSD)
San Diego, California, 92127
UCSD Interventional Psychiatry, 858-207-0938, iptrials@health.ucsd.edu
Greg Appelbaum, PhD
About this study
Official title: Neuronavigated and Non-Neuronavigated Accelerated Intermittent Theta-Burst Stimulation for Treatment-Resistant Depression A Sham-Controlled Randomized Controlled Trial
The purpose of this study is to confirm the efficacy of two recently introduced repetitive transcranial magnetic stimulation (rTMS) interventions - accelerated intermittent theta-burst stimulation (aiTBS) and individualized neuronavigation - in treatment-resistant depression (TRD). Using a three-arm design (neuronavigated aiTBS, non-neuronavigated aiTBS, and sham), this randomized controlled trial (RCT) is the first to specifically investigate the incremental benefit of neuronavigation within an accelerated stimulation protocol, as well as the first confirmatory RCT comparing the efficacy of each of these active treatments vs. sham, overcoming previous generalizability issues and being conducted in an independent, multicenter US TRD sample.
- Conditions
- Treatment Resistant Depression (TRD)
- Being tested
- aiTBS
- Keywords
- depression, TMS
- Medical subject headings
- Depressive Disorder, Treatment-Resistant, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
aiTBSDevice
Repetitive transcranial magnetic stimulation (rTMS) interventions - accelerated intermittent theta-burst stimulation (aiTBS) and individualized neuronavigation.
| Study group | Role | What they receive |
|---|---|---|
| Neuronavigated aiTBS | Experimental | TBS device placement during treatment determined by MRI imaging Receives: Device: aiTBS |
| Non-Neuronavigated aiTBS | Active comparator | Conventional device placement during treatment Receives: Device: aiTBS |
| Sham aiTBS | Sham comparator | identical procedures as the other 2 groups but without turning on the device Receives: Device: aiTBS |
What is being measured
The primary outcome is the main question the study is designed to answer.
HDRS-17 - Depression severity assessment
depression severity as assessed by the Hamilton Depression Rating Scale-17 items (HDRS-17)
Measured: From Baseline visit until week 5 visit
Secondary outcomes (2)
Montgomery-Åsberg Depression Rating Scale (MADRS)
Measured: From Baseline visit until week 5 visit.
Quick Inventory of Depressive Symptoms-Self Report (QIDS-SR)
participant self-rated symptomatology
Measured: From Baseline visit until week 5 visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2026
- Study startJul 2026 (estimated)
- Primary completionJun 2031 (estimated)
- Study completionSep 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Treatment Resistant Depression (TRD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 247 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- University of California, San Diego, Cornell University
- Responsible party
- Principal investigator, Andre Russowsky Brunoni, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07329153
- Sponsor's protocol ID
- STU-2025-1926
- Status last verified
- Jan 2026
- First submitted
- 7 Jan 2026
- Last updated
- 9 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuronavigated and Non-Neuronavigated Accelerated Intermittent Theta-Burst Stimulation for Treatment-Resistant Depression A Sham-Controlled Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07329153
- Acronym / sponsor ID
- STU-2025-1926
- Conditions
- Treatment Resistant Depression (TRD)
- Keywords
- depression, TMS
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 247 participants (estimated)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Collaborators
- University of California, San Diego, Cornell University
- Study start
- Jul 2026 (estimated)
- Primary completion
- Jun 2031 (estimated)
- Study completion
- Sep 2031 (estimated)
- First posted
- 9 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to confirm the efficacy of two recently introduced repetitive transcranial magnetic stimulation (rTMS) interventions - accelerated intermittent theta-burst stimulation (aiTBS) and individualized neuronavigation - in treatment-resistant depression (TRD). Using a three-arm design (neuronavigated aiTBS, non-neuronavigated aiTBS, and sham), this randomized controlled trial (RCT) is the first to specifically investigate the incremental benefit of neuronavigation within an accelerated stimulation protocol, as well as the first confirmatory RCT comparing the efficacy of each of these active treatments vs. sham, overcoming previous generalizability issues and being conducted in an independent, multicenter US TRD sample.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Neuronavigated aiTBS | Experimental | Device: aiTBSTBS device placement during treatment determined by MRI imaging |
| Non-Neuronavigated aiTBS | Active comparator | Device: aiTBSConventional device placement during treatment |
| Sham aiTBS | Sham comparator | Device: aiTBSidentical procedures as the other 2 groups but without turning on the device |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age: 18 to 65 years at the time of consent
- Diagnosis: Current major depressive episode (MDE) in the context of unipolar major depressive disorder (MDD), as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), confirmed by clinical psychiatric interview
- Treatment Resistance: Documented failure to respond to at least two adequate antidepressant trials on the Antidepressant Treatment History Form-Short Form (ATHF-SF). An adequate trial is defined as:
- Depression Severity: Montgomery-Åsberg Depression Rating Scale (MADRS) score >19 at screening, indicating moderate to severe depression
- Medication Stability: No changes in antidepressant medication type or dose for at least 6 weeks prior to randomization. Stable doses of permitted medications must be maintained throughout the trial
Key exclusion criteria (34 listed)
- Any psychiatric disorder other than MDD and comorbid anxiety disorders, including but not limited to:
- Personality disorder confirmed on clinical interview by an experienced study psychiatrist
- Severe suicidal ideation with structured plan (HDRS-17 item 3 score >2) or as determined by the evaluating psychiatrist
- Depressive symptoms better explained by another psychiatric condition, a medical condition, substance use, or use of medications
- Any neurological disorder including but not limited to:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| aiTBSRepetitive transcranial magnetic stimulation (rTMS) interventions - accelerated intermittent theta-burst stimulation (aiTBS) and individualized neuronavigation. | Device | Neuronavigated aiTBS, Non-Neuronavigated aiTBS, Sham aiTBS |
Primary outcome
HDRS-17 - Depression severity assessment
Time frame: From Baseline visit until week 5 visit
depression severity as assessed by the Hamilton Depression Rating Scale-17 items (HDRS-17)
2 secondary outcomes
Montgomery-Åsberg Depression Rating Scale (MADRS)
Time frame: From Baseline visit until week 5 visit.
Quick Inventory of Depressive Symptoms-Self Report (QIDS-SR)
Time frame: From Baseline visit until week 5 visit
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
University of California at San Diego (UCSD)
San Diego, United States
University of Texas Southwestern Medical Center
Dallas, United States
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing aiTBS in people with Treatment Resistant Depression (TRD), run by University of Texas Southwestern Medical Center at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 9 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
HDRS-17 - Depression severity assessment (time frame: From Baseline visit until week 5 visit). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2026.